Key result
Action potential frequency of aortic baroreceptor neurons was lower in diabetic rats compared to controls, an effect reversed by apocynin and tempol.
NADPH oxidase-derived superoxide contributes to blunted aortic baroreceptor neuron excitability in diabetes by enhancing HCN channel activation.
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Should not yet change clinical management of diabetic neuropathy; leaves open whether NADPH oxidase inhibition restores baroreflex function in humans.
NADPH oxidase‐derived superoxide has been identified as key signaling pathway in many pathophysiological processes. Our recent study has indicated that hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channel function is enhanced, which contributes to the blunted aortic baroreceptor (AB) neuron excitability in diabetic state. Therefore, we investigated if NADPH oxidase‐derived superoxide mediates HCN channel activity and cell excitability of AB neurons in streptozotocin (STZ)‐induced diabetic rats. Using western blot and lucigenin chemiluminescence method, we found that protein expression of NADPH oxidase (gp91 phox , p22 phox , p40 phox , p47 phox , and p67 phox ) and superoxide production were higher in nodose ganglia from diabetic rats than that from sham rats. In whole cell patch‐clamp recording, action potential frequency of AB neurons in the diabetic rats was lower than that in the control rats (0.5 ± 0.5 vs. 4.9 ± 0.6 spikes/sec, p<0.05; AB neurons were identified by DiI staining). HCN current density of AB neurons was increased in the diabetic rats, compared with the control rats. In addition, apocynin (30 µM, a NADPH oxidase inhibitor) and tempol (1 mM, a superoxide dismutase mimetic) significantly reduced HCN current density and increased action potential frequency of the AB neurons in diabetic rats. These results indicate that elevation of intracellular NADPH oxidase‐derived superoxide generation contributes to the attenuated AB neuron excitability via enhancing HCN channel activation in diabetic state.
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Zhang et al. (2009) studied Streptozotocin (STZ)-induced diabetes. Apocynin and tempol vs. Control rats / untreated diabetic rats was evaluated on Action potential frequency of aortic baroreceptor neurons (p=<0.05). Action potential frequency of aortic baroreceptor neurons was lower in diabetic rats compared to controls, an effect reversed by apocynin and tempol.
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